J Neurol Neurosurg Psychiatry 1999;67:249–260
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
LETTERS TO
THE EDITOR
Pseudotumour after arteriovenous
malformation embolisation
The association between venous outflow
obstruction and the development of pseudo-
tumour syndrome is well known, although
the mechanism by which the rise in CSF
pressure is brought about is less certain.
Although there is much evidence that the
manifestations are a result of a disturbance of
CSF dynamics, previous reports have focused
solely on a disturbance to absorption. We
present a case in which it is proposed that
alterations in CSF formation, and to a lesser
extent absorption, are responsible for the
development of the syndrome.
At 2 years of age, as part of investigating a
familial pattern of abnormal growth, a female
child underwent cerebral CT. This showed an
unexpected arteriovenous malformation in-
volving the vein of Galen. Although there was
no evidence of cardiac failure or hydrocepha-
lus associated with this, assessment by angio-
graphy was advised. This, initially declined by
the parents, was not undertaken until the age
of 5 years when vertigo and intermittent
numbness of the left arm and leg had been
present for about 12 months.
Angiography showed a deep right temporal
lobe arteriovenous malformation consisting
of three separate fistulae supplied by the right
posterior cerebral and posterior communicat-
ing arteries. These drained into a large
venous varix which subsequently drained into
the Galenic venous system. A cerebral blood
flow study showed a steal syndrome aVecting
the right frontoparietal area, and a decision
was made to attempt embolisation. Complete
occlusion of the fistulae was achieved by
transarterial platinum coil embolisation.
The patient complained of right sided
headache for 24 hours after the procedure,
resolving with minor analgesia. Brain CT the
next day was reported as normal. A full oph-
thalmological review was undertaken before
discharge showing normal fundi and fields.
Ten days after the embolisation the patient
presented with a generalised, pounding head-
ache, present since discharge. Examination
showed mild left papilloedema, with no focal
neurological signs. Brain CT showed a dense
nodule measuring 1.6×1.0 mm above the vein
of Galen and to the right of this (figure). This
was thought to represent the thrombosed
varix and possibly thrombosis of the vein of
Galen and straight sinus. There was no
evidence of hydrocephalus.
At lumbar puncture several days later
opening pressure was 27 cm H2O, with 20 ml
CSF of normal composition withdrawn,
reducing the pressure to 9 cm H2O. Aceta-
zolamide was commenced, and at review 3
weeks later the headaches were settling,
although occasionally present. Examination
was normal; in particular there was now no
evidence of papilloedema.
Cerebral angiography at 3 months con-
firmed obliteration of the fistulae and vein of
Galen and poor filling of the straight sinus
with no evidence of obstruction to major
venous outflow pathways. At this time CSF
pressure, via lumbar puncture, was normal.
Brain CT at level of vein of Galen
demonstrating thrombus.
It is well known that obstruction to a major
portion of the cranial venous outflow can
produce intracranial hypertension, presum-
ably by impairing CSF absorption across the
arachnoid villi.1 In the present case it would
seem that sluggish flow in the venous varix
after embolisation has resulted in thrombosis,
which has propagated to the vein of Galen. As
all investigations seem to have the thrombus
confined to this region, a region of relative
paucity of arachnoid granulations,2 and the
major outflow tracts seem normal, it is
diYcult to accept that impairment of absorp-
tion is the mechanism responsible in the cur-
rent case. An alternative mechanism must be
considered.
It is held that one of the determinants of
the rate of CSF production is the pressure
gradient across the choroid plexus
capillaries.3 Reduction in this pressure has
been shown to decrease the rate of CSF for-
mation, and it is possible that increases in the
transcapillary pressure will, as in other parts
of the body, result in increased transudation
from the capillaries, leading to increased CSF
formation. The malformation in the present
case, haemodynamically important enough to
result in symptoms of steal, and present since
birth, may have resulted in a subnormal tran-
scapillary gradient, and hence a possibly
decreased CSF production. If this were the
case, with decreased production serving to
retard the normal development of absorptive
capacity, then the increase in the pressure in
the choroid plexus capillaries brought about
by both the closure of the fistulae and the
subsequent venous thrombosis may have
resulted in a rate of CSF production greater
than could be handled by the absorptive sys-
tem. Resolution of the thrombus, recruitment
of venous collaterals, and possibly an increase
in absorptive capacity would have resulted in
the resolution of the syndrome.
Dandy and Blackfan,4 in one of the first
experiments of its type, attempted to produce
hydrocephalus in dogs by ligating the vein of
Galen. Their aim was to increase production,
rather than impair absorption, of CSF. Their
failure, a result conclusively demonstrated by
Bedford, was taken to show that venous
obstruction would not result in hydrocepha-
lus. It is, however, worth noting that Bedford5
was able to demonstrate both the fact that
dogs have extensive collaterals in the Galenic
venous system, not present in humans, and
that whereas Galenic venous obstruction
produced little change, obstruction of the
jugular veins resulted in increased CSF
formation. Since these experiments little, if
249
any, work has been done in the area of the
relation between CSF formation and venous
occlusion.
Although the above report is somewhat
speculative, it could serve to explain the facts
which at this stage of our understanding of
CSF dynamics cannot be adequately ac-
counted for. A case of pseudotumor develop-
ing in the setting of minimal venous thrombo-
sis, particularly in part of the venous system
not thought to play a major part in the
absorption of CSF, must force us to recon-
sider our opinions as to the relation between
venous obstruction and CSF dynamics.
This research was supported by the Madeline
Foundation for Neurosurgical Research.
CHRISTOPHER D KOLLAR
Madeline Foundation Laboratory,
University of Sydney, Australia
IAN H JOHNSTON
Department of Neurosurgery, Royal Alexandra
Hospital for Children, Sydney, Australia
Correspondence to: Correspondence to: Dr Chris-
topher Kollar, Madeline Foundation Laboratory,
Room 323, Building D06, University of Sydney
2006, Sydney, Australia. Telephone 0061 2 9351
3359; fax 0061 2 9351 4887;
kollarc@surgery.usyd.edu.au
1 Symonds CP. Hydrocephalic and focal cerebral
symptoms in relation to thrombophlebitis of
the dural sinuses and cerebral veins. Brain
1937;60:531–50.
2 Clark WEL. On the Pacchionian bodies. J Anat
1920;55:40–8.
3 Weiss MH, Wertman N. Modulation of CSF
production by alterations in cerebral perfusion
pressure. Arch Neurol 1978;35:527–9.
4 Dandy WE, Blackfan KD. Internal hydrocepha-
lus. An experimental, clinical and pathological
study. American Journal of Diseases of Children
1914;8:406–82.
5 Bedford THB. The great vein of Galen and the
syndrome of increased intracranial pressure.
Brain 1934;57:1–24.
False negative polymerase chain
reaction on cerebrospinal fluid samples
in tuberculous meningitis established by
culture
The polymerase chain reaction (PCR) has
been reported to be of diagnostic value when
performed on CSF samples in tuberculous
meningitis.1–4 Rapid amplification of Myco-
bacteruim tuberculosis specific DNA enables
results to be available within 48 hours and
can influence treatment decisions.
Recently two patients presented to our
hospital with symptoms and signs suggestive
of tuberculous meningitis. Examination of
CSF disclosed a lymphocytic exudate. Re-
peated samples were sent to a British referral
laboratory where CSF PCR for M tuberculosis
was reported negative. Despite this, antitu-
berculous treatment was continued for 12
months and both patients responded clini-
cally. Several weeks after the negative PCR
result, M tuberculosis was cultured on
Lowenstein-Jensen slopes from CSF taken
from both patients. False negative CSF PCR
in tuberculous meningitis established by cul-
ture has rarely been reported. The two
patients are described to emphasise the dan-
gers of overreliance on PCR in cases of
suspected tuberculous meningitis. Premature
cessation of treatment would have had tragic
consequences for the two patients concerned.
The first patient was a 28 year old Asian
man, last in India 8 years previously. He was
sent from a clinic to hospital for incision and
drainage of two deep seated Staphylococcus
250
aureus abscesses. While an inpatient he com-
plained of headaches and nausea and devel-
oped a low grade pyrexia and meningism.
Brain CT was normal. Lumbar puncture dis-
closed a high opening pressure (19 cm CSF),
133 white blood cells/µl, predominately lym-
phocytes, a raised protein (1.61g/l), and a low
CSF/blood glucose ratio (1.7/6.1). A sample
of 0.5 ml CSF was sent to a British referral
laboratory and PCR for M tuberculosis was
negative. Twenty four hours later, because of
increasing confusion and agitation, treatment
with intravenous acyclovir, antituberculous
chemotherapy (600 mg rifampicin, 300 mg
isoniazid, 2 g pyrazinamide, and 10 mg pyri-
doxine daily), and dexamethasone was com-
menced. Clinically he showed signs of
improvement and was discharged home 2
weeks later on the above treatment. A repeat
lumbar puncture 4 weeks later showed similar
results. A CSF PCR for M tuberculosis was
again negative although a fully sensitive M
tuberculosis grew 12 weeks later from the first
sample on Lowenstein-Jensen slopes.
The second patient was a 21 year old Ken-
yan woman living in the united Kingdom for
3 years. She presented with a 3 month history
of photophobia and occipital headaches. She
had no other systemic symptoms. She had
had peritoneal tuberculosis diagnosed at the
age of 6 years during laparotomy for an
appendicectomy and had received antituber-
culous medication for 1 month only. On
examination she had mild neck stiVness and a
partial left third cranial nerve palsy. Brain CT
was normal. Lumbar puncture results
showed a high opening pressure (15cm CSF),
90 white blood cells/µl, predominantly lym-
phocytes, a raised protein concentration
(1.62 g/l), and a low CSF/blood glucose ratio.
At the same referral laboratory CSF PCR for
M tuberculosis was negative but culture after 8
weeks grew a fully sensitive organism. De-
spite the negative PCR antituberculous
therapy was started empirically. After 2
months of treatment her symptoms had
resolved although a partial third nerve palsy
remains.
Adequate volumes of both patients’ CSF
(0.5 ml) were sent to our referral laboratory
where the samples were spun and PCR
performed using three primer sets and
appropriate controls.5–7 The assay included
primers for the target IS6110, an insertion
sequence normally present in multiple copies
in the M tuberculosis genome, which has been
used successfully for the detection of M
tuberculosis in CSF.2 4 Multiple primer sets
were used as this is thought to increase the
probability of detecting target DNA within a
specimen.
Recent studies suggest that CSF PCR for
M tuberculosis is more sensitive than culture in
cases of clinically suspected tuberculous
meningitis that responded to empirical
treatment.2–4 Some authors have even sug-
gested the usefulness of serial CSF PCR in
assessing the eYcacy of treatment.4 8 False
negatives and positives are rarely reported in
the literature and unless these results are
critically reviewed patients could, tragically,
have treatment prematurely stopped or be
started on prolonged antituberculous chemo-
therapy. False negatives occurred in two
studies, in which reported CSF PCR sensi-
tivities were 32% and 85%.2 3 In one study
6.1% of CSF specimens received from
patients with no evidence of tuberculous
meningitis were falsely PCR positive.3 These
results also show that sensitivity and specifi-
city can vary when diVerent assays and labo-
ratories are used. Claims that PCR can detect
1–10 M tuberculosis organisms “in vitro”
seems not to be the case in clinical samples
such as CSF.
In the two patients presented above
adequate volumes and repeated samples of
CSF were assayed using suitable primers and
appropriate controls at a British referral labo-
ratory. Results for these two patients show the
dangers of overreliance on CSF PCR when
tuberculous meningitis is clinically sus-
pected.
We are grateful to Dr Deborah Binzi-Gascoigne of
the Leeds mycobacterium laboratory, where the
PCR tests were performed and who provided addi-
tional information for the manuscript .
M MELZER
T J BROWN
Department of Microbiology, St Thomas’ Hospital,
Lambeth Palace Road, London SE1 7EH, UK
J FLOOD
S LACEY
L R BAGG
King George Hospital, Barley Lane, Goodmayes, Essex
IG3 8YB, UK
Correspondence to: Dr M Melzer, Department of
Microbiology, St Thomas’ Hospital, Lambeth
Palace Road, London SE1 7EH, UK.
1 Noordhoek GT, Kaan JA, Mulder S, et al. Rou-
tine application of the polymerase chain
reaction for detection of Mycobacterium tuber-
culosis in clinical samples. J Clin Pathol
1995;48:810–14.
2 Nguyen LN, Kox LFF, Pham LD, et al. The
potential contribution of the polymerase chain
reaction to the diagnosis of tuberculous menin-
gitis. Arch Neurol 1996;53:771–6.
3 Seth P, Ahuja GK, Bhanu NV, et al. Evaluation
of polymerase chain reaction for rapid diagno-
sis of clinically suspected tuberculous meningi-
tis. Tuber Lung Dis 1996;77:353–7.
4 Scarpellini P, Racca S, Cinque P, et al. Nested
polymerase chain reaction for diagnosis and
monitoring treatment response in AIDS pa-
tients with tuberculous meningitis. AIDS 1995;
9:895–900.
5 Fauville-Dufaux M, Vanfletern B, De Wit L, et
al. Rapid detection of non-tuberculous myco-
bacteria by polymerase chain reaction amplifi-
cation of 162 base pair DNA fragment from
antigen 85. Eur J Clin Microbiol Infect Dis 1992;
11:797–803.
6 Kolk AH, Schuitema AR, Kuijper S, et al.
Detection of Mycobacterium tuberculosis in
clinical samples by using polymerase chain
reaction and a nonradioactive detection sys-
tem. J Clin Microbiol 1992;30:2567–75.
7 Shankar P, Manjunath N, Laksami R, et al.
Identification of Mycobacterium tuberculosis
by polymerase chain reaction. Lancet 1990;335:
423.
8 Lin JJ, Harn HJ. Application of the polymerase
chain reaction to monitor Mycobacterium
tuberculosis DNA in the CSF of patients with
tuberculous meningitis after antibiotic treat-
ment. J Neurol Neurosurg Psychiatry 1995;59:
175–7.
False negative polymerase chain
reaction on cerebrospinal fluid samples
in tuberculous meningitis
There have been few studies in the literature
concerned solely with the use of the polymer-
ase chain reaction (PCR) to identify Myco-
bacterium tuberculosis DNA directly from
CSF.1–4 These studies suggest that in some
cases, PCR may be more sensitive than
culture; however, in the largest study, per-
formed by Nguyen et al,3 specimens from
seven patients who were culture positive for
M tuberculosis were not positive by PCR. The
study did report on 22 culture negative, PCR
positive patients, suggesting that PCR can be
more sensitive than culture. Studies compar-
ing PCR with culture of M tuberculosis using
Letters, Correspondence, Book reviews
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
other clinical specimens, particularly respira-
tory specimens, have reported that PCR may
be less sensitive than culture for the detection
of M tuberculosis5–9 and that the low sensitivity
correlated with low colony counts on
culture.5 Dalovisio et al6 also reported that
multiple specimens may be required to
improve the sensitivity of the test in some
patients. In the two cases described above,
colonies were seen after incubation for 12 and
8 weeks on LJ slopes, suggesting a low inocu-
lum.
The PCR has been reported to detect the
equivalent of 1–10 mycobacteria in in vitro
testing. However, lower sensitivity is found
with clinical specimens.5 6 The low sensitivity
of PCR may be the result of inhibitors of PCR
present in the reaction, poor lysis of mycobac-
teria, and the uneven distribution of myco-
bacteria in clinical specimens.5 6
D M GASCOYNE-BINZI
P M HAWKEY
Department of Microbiology, The General Infirmary at
Leeds, Great George Street, Leeds LS1 3EX, UK
Correspondence to: Dr D M Gascoyne-Binzi,
Department of Microbiology, The General Infir-
mary at Leeds, Great George Street, Leeds LS1
3EX, UK.
1 Shankar P, Manjunath N, Mohan KK, et al.
Rapid diagnosis of tuberculous meningitis by
polymerase chain reaction. Lancet 1991;337:5–
7.
2 Scarpellini P, Racca S, Cinque P, et al. Nested
polymerase chain reaction for diagnosis and
monitoring treatment response in AIDS pa-
tients with tuberculous meningitis. AIDS 1995;
9:895–900.
3 Nguyen LN, Kox LFF, Pham LD, et al. The
potential contribution of the polymerase chain
reaction to the diagnosis of tuberculous menin-
gitis. Arch Neurol 1996;53:771–6.
4 Seth P, Ahuja GK, Vijaya Bhanu N, et al. Evalu-
ation of polymerase chain reaction for rapid
diagnosis of clinically suspected tuberculous
meningitis. Tuber Lung Dis 1996;77:353–7.
5 Shawar RM, El-Zaatari FAK, Nataraj A, et al.
Detection of Mycobacterium tuberculosis in
clinical samples by two-step polymerase chain
reaction and nonisotopic hybridization meth-
ods. J Clin Micro 1993;31:61–5
6 Dalovisio JR, Montenegro-James S, Kemmerly
SA, et al. Comparison of the amplified
Mycobacterium tuberculosis (MTB) direct
test, Amplicor MTB PCR, and IS6110-PCR
for detection of MTB in respiratory specimens.
Clin Infect Dis 1996;23:1099–6.
7 Garcia JE, Losada JP, Gonzalez Villaron L. Reli-
ability of the polymerase chain reaction in the
diagnosis of mycobacterial infection. Chest
1996;110:300–1
8 Cegielski JP, DevIin BH, Morris AJ, et al. Com-
parison of PCR, culture, and histopathology
for diagnosis of tuberculous pericarditis. J Clin
Micro 1997;35:3254–7.
9 StauVer F, Haber H, Rieger A, et al. Genus level
identification of mycobacteria from clinical
specimens by using an easy-to-handle
Mycobacterium-specific PCR assay. J Clin
Micro 1998;36:614–7.
A novel mutation of the myelin P0
gene segregating Charcot-Marie-Tooth
disease type 1B manifesting as
trigeminal nerve thickening
Charcot-Marie-Tooth disease (CMT) is the
most common type of hereditary peripheral
neuropathy. It is classified into two types
based on pathological and electrophysiologi-
cal findings: type 1 and type 2. CMT type 1
gene loci have been mapped to chromosome
17 (CMT1A), chromosome 1 (CMT1B),1
another unknown chromosome, (CMT1C)
and the X chromosome (CMTX). CMT1B is
a rare form of CMT1 associated with
mutations of the myelin protein zero (P0)
gene. Mutations in the P0 gene have recently
Letters, Correspondence, Book reviews
been recognised in Dejerine-Sottas disease,
peripheral neuropathy with an early onset in
childhood, and a more severe phenotype than
CMT1. CMT1 and Dejerine-Sottas disease
are characterised by thickening of peripheral
nerves, and thickening of the cauda equina,
nerve roots, and ganglia have often been
found.2 3 Although cranial nerves are gener-
ally spared in CMT, thickening of the acous-
tic or optic nerve has been reported in some
cases. We report here on a Japanese patient
who exhibited severe polyneuropathy, bilat-
eral trigeminal thickening on MRI, and an
abnormality of the auditory brain stem
response. Gene analysis disclosed a novel
missense mutation (His81Arg) of P0. The
cranial nerve involvements in this patient may
be associated with the novel missense muta-
tion of P0 (His81Arg).
A 15 year old Japanese girl presented with
CMT disease. She showed delayed motor
development. Although she became ambu-
lant at 1 year and 8 months of age, she was
never able to run. She was referred to our
hospital due to progression of her gait abnor-
mality. Her mentality and higher brain
function were normal. Neurological exam-
ination disclosed weakness in both proximal
and distal muscles of the legs, decreased
grasping power, sensory disturbance of distal
limbs, and generalised areflexia. Facial sensa-
tion, mastication power, and hearing acuity
were normal. She also had atrophy of the
lower limbs, drop foot, a steppage gait, claw
hands and pes cavus deformities. Optic atro-
phy, incoordination, autonomic dysfunction,
and cardiac involvement were not evident.
In laboratory findings, creatinine kinase
was 343 IU/l. A peripheral nerve conduction
study showed undetectable sensory and
motor action potentials in all limbs. Auditory
brain stem response showed abnormal pro-
longation of the I-III interpeak (2.81 ms on
the right side, 2.88 ms on the left side). Brain
MRI (figure) showed significant thickness of
bilateral trigeminal nerves (7 mm) compared
with that of controls (3.15 ± 1.62 mm (mean
± 2 SD), n=20). However, other cranial, spi-
nal nerves and roots were not thick on physi-
cal examination or MRI study. Sural nerve
biopsy was not performed.
Although no detailed familial information
was available, her mother (49 years old)
showed normal findings on neurological
examination and peripheral nerve conduc-
tion study.
Blood samples were obtained from the
patient and her mother with informed
consent. DNA was extracted from the blood
by a standard phenol/chloroform protocol.
Axial T1 weighted (TR 600/TE 15) brain MRI
at 1.5 Tesla of our patient with CMT. Note the
thickness of the bilateral trigeminal nerves.
The six exons of the P0 gene were amplified
by the polymerase chain reaction using prim-
ers, and analysed by single strand conforma-
tional polymorphism (SSCP) and sequencing
analyses. DNA sequencing of exon 3 showed
a novel point mutation (A242 to C at codon 81)
resulting in amino acid substitutions of
arginine for histidine only in the patient. A
DNA duplication in chromosome 17p11.2-
p12, including the peripheral myelin
protein-22 (PMP 22) gene, was not present.
The patient’s mother did not show any muta-
tions in the P0 gene.
CMT type 1 is caused by abnormalities in
myelin protein of Schwann cells. Repeated
demyelinating and remyelinating responses in
the peripheral nerve produce diVusely en-
larged diameters of nerves in CMT type 1,
and thickening of the cauda equina, nerve
roots, and ganglia has also been found.2 3
Although blepharoptosis, ophthalmoplegia,
facial weakness, deafness, dysphagia, and
dysphonia in CMT have been previously
reported,2 clinical involvement in the cranial
nerves is rare and thickening of cranial nerves
has not been reported except for the acoustic
or optic nerves in some cases.
In the present study, our patient showed
severe clinical manifestations of early onset
and undetectable conduction velocities.
Therefore, this patient was considered to
have a severe variant of CMT1 or Dejerine-
Sottas disease. Although her facial sensation,
mastication power, and hearing acuity were
normal, the thickness of bilateral trigeminal
nerves on MRI and prolongation of the I-III
interpeak intervals in auditory brain stem
response were found. The I-III interpeak
interval represents the conduction time from
the eighth nerve to the pontomedullary
portions of the auditory pathway. Prolonga-
tion of the auditory brain stem response sug-
gested peripheral conduction delay of the
auditory nerve.
Trigeminal neuralgia with CMT has been
reported.4 In these rare cases, trigeminal neu-
ralgia was inherited, suggesting a partial
symptom of CMT. Although some patients
were surgically treated, it was not clear
whether a thickened trigeminal nerve was
present. Moreover, on electrophysiological
studies of facial and trigeminal nerves in
CMT, Kimura5 reported that the sensory
component of the trigeminal nerve was
relatively spared, despite extremely delayed
conduction of the facial nerve. However, the
MRI study of our patient suggested that the
fifth cranial nerves were subjected to the same
pathological process that aVects other periph-
eral nerves.
Our patient showed no DNA duplication
on chromosome 17p11.2 and we found a
novel mutation (A to C) representing an
Arg81 to His substitution in the P0 gene. His-
tidine 81 is conserved among many other
species, including cows, rats, chickens, and
sharks. This mutant allele was absent in the
DNA from 100 controls. Therefore we iden-
tified this mutation as pathogenic. Arg81His
was located in exon 3, which codes for the
extracellular domain of P0. The extracellular
domain plays a part in myelin compaction by
homophilic interaction and many mutations
in this area have been reported. Although the
phenotypic variability is related to the
position and nature of the P0 mutation,
patients with cranial nerve involvement are
rare in CMT with a P0 mutation. Therefore,
the unique thickening of trigeminal nerves
and the clinical severity in this patient may
be related to this novel missense mutation. A
251
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
careful comparison of the clinical, electro-
physiological, and histopathological data
between patients with CMT should be
conducted.
We are indebted to the families studied for their
cooperation and support. This work was partly sup-
ported by Uehara Memorial Foundation, the Sasa-
kawa Health Science Foundation, the Primary
Amyloidosis Research Committee, and the Ministry
of Education, Science and Culture of Japan
10832002, 18832993.
MASAMI SHIZUKA
YOSHIO IKEDA
MITSUNORI WATANABE
KOICHI OKAMOTO
MIKIO SHOJI
Department of Neurology, Gunma University School of
Medicine, 3–39–22 Showa-machi, Maebashi, Gunma
371–8511, Japan
TORU IKEGAMI
KIYOSHI HAYASAKA
Department of Pediatrics, Yamagata University School
of Medicine, Yamagata, Japan
Correspondence to: Dr Masami Shizuka, Depart-
ment of Neurology, Gunma University School of
Medicine, 3–39–22 Showa-machi, Maebashi,
Gunma 371–8511, Japan. Telephone 0081 27 220
8061;fax 0081 27 220 8068;email
mshizuka@news.sb.gunma-u.ac.jp
1 Hayasaka K, Himoro M, Sato W, et al. Charcot-
Marie-Tooth neuropathy type 1B is associated
with mutations of the myelin P0 gene. Nat Genet
1993;5:31–4.
2 Tyson J, Ellis D, Fairbrother U, et al. Hereditary
demyelinating neuropathy of infancy: a geneti-
cally complex syndrome. Brain 1997;120:47–
63.
3 Choi SK, Bowers RP, Buckthal PE. MR
imaging in hypertrophic neuropathy: a case of
hereditary motor and sensory neuropathy, type
I (Charcot-Marie-Tooth). Clin Imaging 1990;
14:203–7.
4 CoVey RJ, Fromm GH. Familial trigeminal
neuralgia and Charcot-Marie-Tooth neu-
ropathy. Report of two families and review.
Surg Neurol 1991;35:49–53.
5 Kimura J. An evaluation of the facial and
trigeminal nerves in polyneuropathy: Electro-
diagnostic study in Charcot-Marie-Tooth dis-
ease, Guillain-Barré syndrome, and diabetic
neuropathy. Neurology 1971;21:745–52.
Intracranial extracerebral follicular
lymphoma mimicking a sphenoid wing
meningioma
Primary lymphoma in the brain is uncom-
mon, accounting for only 2% of primary
intracranial neoplasms,1 although its inci-
dence seems to be dramatically increasing.2
Leptomeningeal lymphomas are even rarer
but have been described1 3 4; however, no lep-
tomeningeal lymphoma of the follicular type
has previously been reported. We present a
case of a primary meningeal follicular
lymphoma which mimicked a sphenoid wing
meningioma, both radiologically and intraop-
eratively.
A 57 year old Ghanaian woman was
referred with a 3 year history of worsening
bitemporal headache, followed by a 6 month
history of daily right frontal headache lasting
for 2–3 hours associated with mild photopho-
bia. There were no reports of seizures,
nausea, or other visual disturbances. Her
medical history was 3 years of treated hyper-
tension, sickle cell carrier trait, and a cataract
extraction. The patient was obese but physi-
cal examination was otherwise normal.
Neurological examination showed no papil-
loedema and there were no cranial nerve or
long tract signs.
Brain CT showed an enhancing mass con-
sistent with a right sided sphenoid wing
252
(A) Contrast enhanced CT of the head showing
a 6×4×6 cm enhancing mass lesion in the region
of the right lesser sphenoid wing. (B, C)
Photomicrographs of the surgical specimen. (B)
Section through the lesion showing irregular, ill
defined lymphoid follicles. Haematoxylin and
eosin, original magnification×30. (C) Follicle
centre composed of a mixture of centrocytes and
centroblasts with mitotic activity (arrow).
Haematoxylin and eosin, original
magnification×500.
meningioma (figure A). Right pterional
craniotomy was performed and a tumour
located under and adherent to the overlying
dura was identified. It was entirely extracer-
ebral, measuring 6×4×6 cm, with the greyish
colour and hard consistency typical of a
meningioma. The tumour and the adherent,
thickened dura was macroscopically com-
pletely removed.
Histologically the lesion consisted of lym-
phoid tissue with an ill defined follicular
architecture (figure B). The follicles varied in
size and shape and infiltrated the overlying
dura. Follicular centres were composed of a
mixture of centrocytes and centroblasts with
frequent mitotic figures and apoptotic bodies
(figure C). Immunohistochemical staining
confirmed that these cells had a B lym-
phocytic phenotype (CD20 positive) with
kappa light chain restriction. Staining for
Bcl-2 protein, which is an inhibitor of
apoptosis and is expressed in 90% of follicu-
lar lymphoma, was found to be positive. The
histological appearances and immunohisto-
chemical profile confirmed a follicular
lymphoma.
The patient made an uneventful recovery
and was referred for staging investigations
and consideration of postoperative therapy.
An LDH estimation was within normal limits
and HIV serology was negative. Whole body
CT including repeat CT of the brain did not
show any evidence of lymphadenopathy or
lymphomatous deposit. Bone marrow exam-
ination was declined. Postoperative adjuvant
whole brain or localised radiotherapy was
discussed with the patient, however, she
declined any further intervention. She has
been closely reviewed in the follow up clinic
and after 6 months there has been no clinical
or radiological evidence of relapse.
Primary intracerebral lymphomas repre-
sent about 2% of intracranial neoplasms and
2% of all lymphomas. They occur most com-
monly in the 6th decade of life with a female
to male ratio of roughly 2:1.1 The association
between primary intracranial lymphoma and
immunodeficiency has long been established,
and it is not surprising, therefore, that the
incidence has increased 10-fold over the past
3 decades with the onset of transplant surgery
and, particularly the AIDS epidemic.2 In
postmortem studies, these neoplasms are
found, on average, in 5.5% of AIDS cases,
and malignant cerebral lymphoma is the most
common diagnosis of a focal intracranial
lesion in patients with AIDS.1 3 Malignant
primary lymphoma can occur throughout the
CNS and they often have a periventricular
distribution. Multifocality seems to be more
common in patients with AIDS. The CT scan
usually shows hyperdense masses with peritu-
morous oedema and 92% enhance after
administration of contrast medium.1
Leptomeningeal lymphoma is usually en-
countered as a late complication of systemic
non-Hodgkin’s lymphoma, although primary
leptomeningeal lymphoma is occasionally
seen. The prognosis for these tumours is
poor.4 DiVuse intracranial lymphomas have
been mistaken for more common lesions:
solitary primary B cell lymphoma of the cer-
ebellopontine angle mimicking acoustic neu-
rilemoma or meningioma has been reported5;
Vigushin et al6 reported a patient with a calci-
fied temporoparietal lymphoplasmacytic
lymphoma which resembled a meningioma;
however, this tumour was entirely extradural.
There is only one previous report of a follicu-
lar rather than diVuse intracranial lymphoma:
Rubinstein7 described a case of follicular
lymphoma metastasis found in the dura of a
61 year old man at necropsy.
We found no report of a primary follicular
extracerebral lymphoma. Similar radiological
and intraoperative appearances of the tumour
in our case to sphenoid wing meningioma
suggest that this entity should be considered
as a rare diVerential diagnosis.
We thank Professor Francesco Scaravilli, National
Hospital for Neurology and Neurosurgery and Dr
Mark Napier, The Meyerstein Institute of Oncol-
ogy, Middlesex Hospital, for their help with this
report.
DOMINIC J HODGSON
KAROLY M DAVID
MICHAEL POWELL
Department of Surgical Neurology
JAN L HOLTON
Department of Neuropathology, The National Hospital
for Neurology and Neurosurgery
FRANCESCO PEZZELLA
Department of Pathology, University College Hospital,
London, UK
Letters, Correspondence, Book reviews
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
Correspondence to: Mr Michael Powell, Depart-
ment of Surgical Neurology, The National Hospital
for Neurology and Neurosurgery, Queen Square,
London, WC1N 3BG, United Kingdom. Telephone
0044 171 837 3611; fax 0044 171 209 3875.
1 Lantos PL, Vandenburg SR, Kleihues P. Tu-
mours of the nervous system. In: Graham DI,
Lantos PL, eds. Greenfield’s pathology. 6th ed.
London: Arnold 1997:766–75.
2 Corn BW, Marcus SM, Topham A, et al. Will
primary central nervous system lymphoma be
the most frequently diagnosed brain tumor by
the year 2000? Cancer 1997;79:2409–13.
3 Russell DS, Rubinstein LJ, eds. Nervous system
involvement by lymphomas, histiocytes and
leukaemias. In: Pathology of tumours of the nerv-
ous system. 5th ed. London: Edward
Arnold,1989:590–615.
4 Lachance DH, O’Neill BP, Macdonald DR, et
al. Primary leptomeningeal lymphoma: report
of nine cases, diagnosis with immunocyto-
chemical analysis, and review of the literature.
Neurology 1991;41:95–100.
5 Shuangshoti S. Solitary primary lymphoma of
the cerebellopontine angle: Case report. Neuro-
surgery 1995;36:595–8.
6 Vigushin DM, Hawkins PN, Hsuan JJ, et al.
ALê amyloid in a solitary extradural
lymphoma. J Neurol Neurosurg Psychiatry 1994;
57:751–4.
7 Rubinstein M. Cranial mononeuropathy as the
first sign of intracranial metastasis. Ann Intern
Med 1970;70:49–54.
Determinants of the copper
concentration in cerebrospinal fluid
The measurement of CSF copper concentra-
tion can serve as an indicator of brain copper
concentration.1 2 However, the complex
mechanisms by which copper crosses into the
CSF, and the factors determining the CSF
copper concentration in humans are largely
obscure. Copper can pass into and out of the
CSF by various mechanisms. For example,
active transport through the blood-brain bar-
rier or the blood-CSF barrier, or passive dif-
fusion of the free or the bound fraction
(bound to albumin or coeruloplasmin)
through the blood-CSF barrier. We studied
the factors influencing CSF copper concen-
tration using a stepwise multiple linear
regression model. The independent variables
were age, plasma coeruloplasmin, CSF/
serum albumin ratio, total serum copper
concentration, and calculated serum free
copper concentration (based on serum
coeruloplasmin and total serum copper con-
centration). The CSF copper concentration
was treated as a dependent variable of
continuous type. We investigated lumbar
CSF samples from 113 patients. These
patients had dementia, extrapyramidal, or
tremor symptoms; lumbar puncture was per-
formed to exclude Wilson’s disease, and none
of the patients had the disease. Copper was
measured by flameless atomic absorption
(Perkin Elmer, HGA 500, Ueberlingen, Ger-
many). Coeruloplasmin was determined
nephelometrically (Beckman Array: Beck-
man Instruments, Brea, CA, USA). The age
of the patients was 50.0 (SD15.5) years; 50
were women and 63 were men. Mean serum
coeruloplasmin concentrations were 394.3
(SD 11.7) mg/l. Mean serum copper concen-
trations were 1194 (SD 335) µg/l. Mean calcu-
lated free copper concentrations in serum
were 78.5 (SD 1285) µg/l. Mean CSF copper
concentrations were 14.16 (SD 6.0) µg/l. The
mean albumin ratio (AR) was 6.63×10−3. The
mean ratio of calculated serum free copper
concentration to total serum copper was
6.6%, the ratio of CSF copper to serum
copper was 1.2%, and the ratio of free serum
copper to CSF copper was 18%. In the
Letters, Correspondence, Book reviews
1.6
1.5
1.4
CSF/copper (µg/l, log)
1.3
1.2
1.1
1.0
0.9
0.8
0.7
0.2 0.4 0.6 0.8 1.0 1.2
Albumin ratio (CSF/serum, log)
Correlation of blood-CSF barrier (albumin ratio,
(AR)) with total CSF copper concentration (on
logarithmic axes). R=0.46, p=0.0001; 95%
confidence bands for the true mean of the total
CSF copper concentration are shown.
stepwise linear regression model (F to enter
4.0, F to remove: 3.996), significant positive
predictors of the CSF copper concentration
were found to be AR (p=0.0001) and serum
coeruloplasmin (p=0.0057). The other inde-
pendent variables mentioned above showed
no statistically significant relation with CSF
copper concentration. The figure shows the
simple linear regression between CSF/serum
albumin ratio and CSF copper concentration
(on logarithmic axes; R=0.46, p=0.0001).
The formula for the CSF copper concentra-
tion, derived from the multiple linear
regression model, is: copper CSF (µg/l)=5.32
µg/l±0.653 × CSF/serum albumin ratio
(×10−3)+0.012×serum coeruloplasmin (mg/
l). According to this analysis,CSF/serum
albumin ratio and serum coeruloplasmin
together determine 25.3% of the variation in
CSF copper concentration (adjusted
R2=0.253), implying that other (unknown)
factors determine the remaining 74.7% of the
variation. We have been able to demonstrate
here that the CSF copper concentration is
determined in a highly significant manner by
disturbances in the blood-CSF barrier and by
the serum coeruloplasmin concentration. It
can be assumed from this that in the case of
normal blood-CSF barrier function and a
normal serum coeruloplasmin concentration,
29.7% of the measured CSF copper entered
the CSF by passive diVusion bound to coeru-
loplasmin, and only around 0.09% by passive
diVusion bound to albumin. In the case of a
markedly raised CSF/serum albumin ratio of
20×10−3, this would mean that 60.6% of the
measured CSF copper originated from the
blood (bound to coeruloplasmin). A variable
fraction of the CSF copper concentration,
depending on the degree of damage to the
blood-CSF barrier, therefore crosses from
the blood into the CSF and can be measured
there. Our formula would therefore predict,
in patients with Wilson’s disease with anin-
tact blood-CSF barrier (assuming a CSF/
serum albumin ratio of 6.5×10−3), that the
CSF copper concentration is actually re-
duced by 27.4%, when the serum coerulo-
plasmin concentration falls from its normal
value of 394 mg/l to 68 mg/l. In consequence,
CSF copper in patients with Wilson’s disease
is evidently substantially free, implying that a
larger fraction than previously assumed of the
raised CSF copper in patients with untreated
Wilson’s disease originates from the brain;
the fraction entering the CSF by passive dif-
fusion (bound to coeruloplasmin) tends
towards zero. It can be concluded from this
that, when the aim of therapy is considered in
terms of the total CSF copper concentration,
a region around 30% lower than the upper
limit of the normal range should be aimed
for. This is supported by the clinical finding
that patients report feeling better when the
CSF copper concentration is below this
value. This analysis also shows that the raised
copper concentration in the CSF can only
originate from the brain. In particular, it is
not associated with free serum copper, but
evidently only via storage in the brain. The
investigation here also shows that, after
determining the CSF copper concentration,
the coeruloplasmin-bound fraction originat-
ing from the plasma should be subtracted
1.4 1.6
according to the formula we have given, or
better, all measured copper concentrations in
the CSF should be adjusted using the
CSF/serum albumin ratio and serum coeru-
loplasmin concentration. A statistical relation
with a low correlation (p<0.05) between CSF
protein content and CSF copper was already
shown in 1989 in various neurological
diseases3; our study shows a much higher sig-
nificance and, in addition, the eVect of serum
coeruloplasmin (therefore of bound serum
copper). Furthermore, we have been able to
determine quantitatively the fraction of CSF
copper which enters the CSF across the
blood-CSF barrier.
HANS JOERGSTUERENBURG
MATTHIAS OECHSNER
SVEN SCHROEDER
KLAUS KUNZE
Neurological Department, University Hospital
Hamburg-Eppendorf, Germany
Correspondence to: Dr Hans Joerg Stuerenburg,
Neurological Department, University Hospital
Hamburg-Eppendorf, Martinistrasse 52, 20246
Hamburg, Germany. Telephone 0049 40 4717
4832; fax 0049 40 4717 5086.
1 Kodama H, Okabe I, Yanagisawa M, et al. Does
CSF copper level in Wilson disease reflect cop-
per accumulation in the brain. Pediatr Neurol
1988;4:35–7.
2 Weisner B, Hartard C, Dieu C. CSF copper
concentration: a new parameter for diagnosis
and monitoring therapy of Wilson’s disease
with cerebral manifestation. J Neurol Sci 1987;
79:229–37.
3 Kapaki E, Segditsa J, Papageorgiou C. Zinc,
copper and magnesium concentration in serum
and CSF of patients with neurological disor-
ders. Acta Neurol Scand 1989;79:373–8.
Solitary intracranial myofibroma in a
child
A rare case of solitary interhemispheric
myofibroma with excellent outcome in a 20
month old boy is described. The clinico-
pathological features of this unusual condi-
tion are reviewed with emphasis on the CNS
manifestations.
A case of congenital fibrosarcoma was first
diagnosed by William and Schrum1 and was
subsequently renamed congenital generalised
fibromatosis by Stout in 19542 as a distinct
form of juvenile fibromatosis characterised by
tumour-like nodules involving the skin, soft
tissues, bones, and viscera. Based on the
ultrastructural and immunohistochemical
features of the cell of origin and the
occurrence of this condition in infants, as well
as congenitally, it was renamed infantile
myofibromatosis by Chung and Enzinger in
1981.3 This disorder is considered to repre-
sent a hamartomatous myofibroblastic prolif-
253
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
eration, although laboratory evidence
suggests that it may arise secondary to
oestrogen stimulation in utero. Infantile
myofibromatosis represents the most com-
mon fibrous tumour of infancy and may
present with solitary or multicentric lesions.
When visceral involvement is present, the
multilesional form is termed “generalised”.
Cases with familial incidence,3 spontaneous
regression,4 5 and fatal outcome3 6 have all
been described. Poor outcome has generally
been associated with extensive visceral in-
volvement and relates either to mass eVect
with compression of vital organs and struc-
tures, or to pulmonary involvement, when
subintimal or submucosal cellular prolifera-
tion results in vascular or bronchial
obliteration.2
Central nervous system involvement is
exceptionally rare and has been reported as a
finding in the multicentric type of
myofibromatosis.6–9 We describe a solitary
interhemispheric myofibroma which pre-
sented as an intracranial mass in a 20 month
old child. To our knowledge, only one other
case of solitary intracranial myofibroma has
been reported.10
A 20 month old Irish boy, the only son of
healthy, unrelated parents, was admitted for
investigation of a large head. He had one pre-
vious hospital admission at the age of 6 weeks
for a respiratory tract infection. Transient
muscle hypotonia was noted at that time as
was his skull circumference of 43 cm. At 6
months there was no hypotonia, neurological
examination was normal, and the head
circumference was 49 cm. The father’s head
circumference was 61 cm and he stated that
all of his family had “big heads”. By 20
months, the patient’s head circumference
measured 55.6 cm and was diverging from
the 97th centile. Brain CT showed a well cir-
cumscribed, contrast enhancing mass in the
midline and left frontal lobe, with surround-
ing oedema. There was evidence of left sided
hydrocephalus due to displacement of the
right foramen of Munro by tumour. The
radiological diVerential diagnosis included a
primary meningeal tumour, glioma, and leu-
kaemic deposit. The patient underwent a left
frontal craniotomy and a firm, rounded mass
was removed from between the hemispheres.
The mass was not attached to the falx, but
was firmly adherent to the left pericallosal
artery. A fragment (4 mm×2 mm) had to be
left attached to the vessel. Postoperatively, he
had transient paresis of the right leg, which
subsequently resolved completely. Repeat CT
6 months later and at 4 years after the opera-
tion showed no evidence of recurrence or
mass eVect. His head circumference persisted
on the 97th centile 4 years after operation.
His development and clinical examination
otherwise remain normal 6 years after
surgery. A younger sibling is normal.
The rounded 3.0 cm mass had a whorled,
fibrous, white-yellow cut surface appearance.
Microscopically, it consisted of hypercellular
fasciculated and storiform areas, alternating
with hypocellular, hyalinised regions. Cen-
trally a haemangiopericytoma-like pattern
was seen. No mitotic figures were present and
there was no evidence of haemorrhage,
necrosis, or calcification. The tumour cells
appeared to blend with the vessel walls.
Immunohistochemical studies showed strong
reactivity for vimentin and smooth muscle
actin. Scattered cells showed immunoreactiv-
ity for desmin. No reactivity was noted for
cytokeratin, epithelial membrane antigen,
factor VIII, glial fibrillary acidic protein, or
254
myoglobin. Ultrastructural examination
showed elongated cells with surrounding
collagen fibrils, some showing intracytoplas-
mic myofilaments.
Solitary lesions of infantile myofibromato-
sis are more common than multiple lesions,
with twice as many males as females being
aZicted, and generally involve the skin and
soft tissues, especially of the head and neck.2
Solitary lesions are less commonly found in
viscera or bones.11 Involvement of the CNS is
exceedingly rare and only one other case of a
solitary mass is reported10 along with few
cases of CNS involvement in the generalised
form of infantile myofibromatosis.6–9 11–13 The
prognosis is best for cases with solitary
masses and less favourable for multicentric
cases, particularly where visceral lesions are
present, in which morbidity and mortality
derive predominantly from pulmonary in-
volvement or mass eVect.
The diVerential diagnosis for this lesion
included meningioma, schwannoma, and
haemangiopericytoma. Regionally, the histol-
ogy was reminiscent of the rare microcystic
variant of meningioma. Meningiomas are
extremely rare in this age group, this lesion
was not meningeal based and such lesions are
usually reactive for epithelial membrane anti-
gen unlike this tumour. This lesion, unlike
schwannomas, showed no immunoreactivity
for S-100 protein. Haemangiopericytoma is a
diagnosis of exclusion and shows no reactivity
for actin, unlike this tumour.
Prior reports of intracranial involvement by
myofibromatosis include patients with wide-
spread systemic involvement and multiple
leptomeningeal nodules6 in one patient and
extradural masses in another,8 both of which
were fatal at the age of 10 days, a non-fatal7
extradural mass in one patient, and a patient
with systemic involvement, in which there
was recurrence of orbital and temporal
lesions 2 years after operation. A single previ-
ous case of solitary intracranial myofibroma
has been reported10 in which the patient died
within 24 hours of surgery, secondary to car-
diorespiratory arrest.
We present a patient with a solitary intrac-
ranial myofibroma with an excellent postop-
erative outcome. Although rare, infantile
myofibroma should be included in the diVer-
ential diagnosis of intracranial neoplasms in
children.
We acknowledge the expert assistance of Drs Lucy
Roarke and Dr Louis Dehner in diagnosing this
case.
C B O’SUILLEABHAIN
C J MARKS
Department of Neurosurgery
D RYDER
Department of Radiology
C KEOHANE
M J O’SULLIVAN
Department of Pathology,University College Cork,
Cork University Hospital, Wilton, Cork, Ireland
Correspondence to: Dr. M.J. O’Sullivan, Lauren V
Ackerman Laboratory of Surgical Pathology, Wash-
ington University Medical Center, PO Box 8118,
660, South Euclid Avenue, St Louis, MO 63110,
USA. Telephone 001 314 362 0101; fax 001 314
362 8950.
1 William JO, Schrum D. Congenital fibrosar-
coma. Report of case in newborn infant. AMA
Arch Pathol 1951;51:548–52
2 Stout, A.P. Juvenile fibromatosis. Cancer 1954;7:
953–78.
3 Chung EB, Enzinger FM. Infantile myofi-
bromatosis. Cancer 1981;48:1807–18.
4 Maude R, Hennequet A, Loubry P, et al.
Fibromatose congentiale diVuse du
nouveau-ne a evolution regressive. Ann Paedi-
atr (Paris) 1965;12:692–7.
5 Teng P, Warden MJ, Cohn WL. Congenital gen-
eralized fibromatosis (renal and skeletal) with
complete spontaneous regression. J Paediatr
1963;62:748–53.
6 Zschoch H, Poley F. Angeborene generalisierte
Fibromatose. Zentralblatt algemeiner Pathologie
1972;116:279–86.
7 Dimmick JE, Wood WS. Congenital multiple
fibromatosis. Am J Dermatopathol 1983;5:289–
95.
8 Adickes ED, Goodrich P, AuchMoedy J, et al.
Central nervous system involvement in con-
genital visceral fibromatosis. Pediatr Pathol
1985;3:329–40.
9 Salamah MM, Hammoudi SM, Sadi ARM.
Infantile myofibromatosis. J Pediatr Surg 1988;
23:975–7.
10 Cardia E, Molina D, Zaccone C, et al. Intracra-
nial solitary-type infantile myofibromatosis.
Childs Nerv Syst 1993;9:246–9.
11 Wiswell TE, Sakas EL, Stephenson SR, et al.
Infantile myofibromatosis. Pediatrics 1985;76:
981–4.
12 Altemani AM, Amstalden EI, Martins Filho J.
Congenital generalized fibromatosis causing
spinal compression. Hum Pathol 1985;16:
1063–5.
13 Enzinger F, Weiss S. Fibrous tumors of infancy.
In: Soft tissue tumors. St Louis: Mosby Year
Book Inc, 1995:238–45.
Axonal polyneuropathy and
encephalopathy in a patient with
verotoxin producing Escherichia coli
(VTEC) infection
Escherichia coli serotype O157:H7 causes
serious food poisoning worldwide, especially
in children and elderly people.1 It is also
called verotoxin producing E coli (VTEC),
which produces a cytotoxic Shiga-like toxin.
Gastrointestinal, haemorrhagic, and uraemic
eVects are well known in VTEC infection,2
and neurological problems are likely to be
more frequent than is generally recognised.3
Here we describe axonal polyneuropathy and
encephalopathy in a young female patient
associated with haemolytic-uraemic syn-
drome caused by VTEC infection.
A 26 year old woman began to have
abdominal pain and haemorrhagic diarrhoea.
She was admitted to an emergency hospital
and diagnosed as having haemorrhagic colitis
due to probable food poisoning. Then her
urinary volume gradually decreased and
serum creatinine increased, and she was
transferred to our hospital. On the 9th day
she had a high fever of 39.7°C with increased
C reactive protein of 7.6 mg/l and a leukocy-
tosis of 17 800/mm3. She was in a state of
anuria and her blood analysis showed severe
kidney dysfunction (increased serum creati-
nine of 6.76 mg/l). She had severe anaemia
(haemoglobin 6.0 g/dl), fragmentation, and
tear drop deformation of red blood cells in
the blood smear and increased lactate dehy-
drogenase concentration of 4095 IU (normal
range 230–460 IU), suggestive of haemolytic
anaemia. Her platelet count was decreased to
21 000/mm3. The culture of her stool showed
the growth of E coli O157:H7 and analysis of
the bacterial toxins showed the presence of
verotoxin, which confirmed the diagnosis of
VTEC infection. She was given plasma
exchange, continuous haemodialysis, and
antibiotics (4 g/day fosfomycin, 600 mg/day
levofloxacin, and 2 g/day cefoperazon/
sulbactam). Her general status was un-
changed for 1 week after admission and she
was in a delirious state with visual hallucina-
tions and tonic convulsion, indicative of
encephalopathy. Brain CT disclosed mild
brain swelling and there were diVuse slow
waves in the frontal area on EEG. She was
Letters, Correspondence, Book reviews
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
given 250 mg/day diphenylhydantoin. During
the next two weeks her kidney function,
haemolytic anaemia, and encephalopathy
gradually improved.
After recovery of consciousness she began
to complain of numbness of the limbs, mani-
fest in the legs. She described her feet as feel-
ing like frost bite when she was lying on the
bed, and this gradually exacerbated to be a
burning pain. On examination she was alert
and cooperative. Her cranial nerves were
normal. Muscle strength was normal and
coordination was intact. Deep tendon re-
flexes were decreased in the four limbs. Sen-
sation for vibration was impaired in the lower
legs, but preserved for pin prick, light touch,
and joint sensation. Routine laboratory data
including haematological studies, serum
chemistry, urinalysis, and CSF analysis were
normal. Serum concentrations of vitamin B1,
B6, and B12 were normal. Nerve conduction
studies were carried out on her right limbs,
and showed normal findings in the distal
latencies, motor conduction velocities, and F
wave latencies of the median, ulnar, and tibial
nerves, and no evidence of conduction block.
However, there were decreased compound
muscle action potentials (1.18 mV) and mild
slowing of motor conduction velocity (41.0
m/s) in the peroneal nerve. There were also
markedly decreased amplitudes of the sen-
sory nerve action potentials in the ulnar (6.46
µV) and sural (0.98µV) nerves. These find-
ings and the clinical features confirmed the
diagnosis of sensory dominant, axonal
polyneuropathy. She was given 300 mg/day
sulindac (an anti-inflammatory agent) and
1500 µg/day mechobalamin (vitamin B12)
without eVect. Two weeks after administra-
tion of 300 mg/day oral mexiletin, her numb-
ness and pain gradually disappeared.
The patient was diagnosed as having
VTEC infection, because of a typical history
of an acute haemorrhagic colitis, the cultured
growth of enterohaemorrhagic E coli
O157:H7, and the detection of verotoxin in
her stool. She had haemolytic-uraemic syn-
drome (haemolytic anaemia, thrombocytope-
nia, and uraemia, following diarrhoea), which
is the main complication of VTEC infection.
Experimentally, vero cells, an immortalised
primate kidney cell line, are killed by low
doses of verotoxin through the process of
apoptosis.1 2 Verotoxin shows similar cytotox-
ity on human glomerular microvascular
endotherial cells via inflammatory mediators
such as tumour necrosis factor-á, which
induced an increase in the numbers of
verotoxin receptors, leading to a microvascu-
lar thrombosis.2 Our patient was treated with
antibiotics, plasma exchange, and continuous
haemodialysis, with benefit.
During the course of the disease, our
patient was in a delirious state with visual
hallucinations and tonic convulsion. She
showed mild brain swelling on CT and
diVuse slow waves in the frontal area on EEG,
evidence of encephalopathy. Previous reports
have shown that the incidence of encepha-
lopathy in haemolytic-uraemic syndrome
(mostly of VTEC infection) is 30% to 52%,3
including seizures in 17%–44%, altered con-
sciousness in 7%–40%, and paralysis in
1%–16%. Many of the patients, including
ours, seemed to have metabolic encephalopa-
thy, but some developed encephalopathy
without metabolic abnormalities.3 There is
experimental evidence that verotoxin has
direct virulence to both endotherial cells and
neurons in the nervous system, and its initial
lesion is in the hypothalamic areas, then
Letters, Correspondence, Book reviews
spreading into the hippocampus and the
brainstem.4 The convulsions in our patient
was successfully treated with 250 mg/day
diphenylhydantoin, and her encephalopathy
gradually improved during plasma exchange
and haemodialysis.
After recovering consiousness, she began to
complain of numbness of her limbs, and a
burning pain which exacerbated in the night.
Nerve conduction studies and the clinical
features confirmed the diagnosis of sensory-
dominant, axonal polyneuropathy. At this
stage metabolic abnormalities were not de-
tected and serum concentrations of vitamins
B1, B6, and B12 were normal. Her numbness
and tingling sensation ameliorated after 2
weeks administration of 300 mg/day oral
mexiletin, an agent with a membrane stabilis-
ing eVect. Up to now, to our knowledge,
peripheral neuropathy has not been reported
in VTEC infection other than in one patient,
by Hamano et al,5 who showed bilateral
phrenic nerve palsy for 2 weeks after recover-
ing consiousness. The above experimental
evidence suggests that microcircular distur-
bance or direct toxicity to the neuronal cells
by verotoxin could cause axonal neuropathy
in VTEC infection.
RYUJI SAKAKIBARA
TAKAMICHI HATTORI
KEIKO MIZOBUCHI
SATOSHI KUWABARA
Department of Neurology
MITSUGU OGAWA
First Department of Internal Medicine, Chiba
University, 1–8–1 Inohana Chuo-ku, Chiba 260,
Japan
Correspondence to: Dr Ryuji Sakakibara, Depart-
ment of Neurology, Chiba University, 1–8–1
Inohana Chuo-ku, Chiba 260, Japan.
1 Cola JE. Clinical, microbiological and epide-
miological aspects of Escherichia coli O157
infection. FEMS Immunol Med Microbiol
1998;20:1–9.
2 Arbes GS. Association of verotoxin-producing
E. coli and verotoxin with hemolytic uremic
syndrome. Kidney Int 1997;51(suppl):S91–6.
3 Sheth KJ, Swink HM, Haworth N. Neurological
involvement in hemoyltic-uremic syndrome.
Ann Neurol 1986;19:90–3.
4 Fujii J, Yoshida S. Magnetic resonance imaging
and histopathological study of brain lesions in
rabbits given intravenous verotoxin 2. Infect
Immun 1996;64:5053–60.
5 Hamano S, Nakanishi Y, Nara T. Neurological
manifestations in hemorrhagic colitis associ-
ated with Escherichia coli O157:H7. No To
Hattatsu 1992;24:250–6. (In Japanese with
English abstract.)
Crying spells as symptoms of a be a manifestation of a transient ischaemic
transient ischaemic attack
In the absence of depression, crying spells
associated with neurological disease usually
result from pseudobulbar palsy or, more
rarely, from crying seizures. To our knowl-
edge, there are no prior reports of crying
spells heralding or signifying a transient
ischaemic attack. We report on a patient with
prominent cerebrovascular risk factors who
had a transient episode of intractable crying
and focal neurological findings.
The patient was a 55 year old right handed
man who presented with acute, uncontrolled
crying spells followed by left sided paraesthe-
sias. Around 6 00 am he awoke with a diffuse,
pressure headache and suddenly started cry-
ing for no apparent reason. There was no
accompanying feeling of sadness. This cry-
ing, which involved lacrimation and “sob-
bing,” abruptly ceased after 5 minutes.
Within 30 minutes of his initial crying spell,
his headache had resolved but he became
aware of numbness over his left face and
numbness and pain in his left neck and arm.
The numbness was not progressive, and the
patient did not complain of paraesthesias in
his trunk or left leg. He denied photophobia,
nausea or vomiting, blurred vision, visual
obscurations, diYculty swallowing, dysar-
thria, or focal weakness. Over the next 2 to 3
hours, he had five more crying spells, each
lasting 5 to 10 minutes, occurring out of con-
text, without precipitating factors or sadness,
with an acute onset and oVset, and without
alteration of consciousness. The patient’s left
face and arm numbness persisted during and
between these crying spells but abruptly
resolved shortly after his last crying spell.
This patient had hypertension, diabetes mel-
litus, coronary artery disease, an old myocar-
dial infarction, raised cholesterol concentra-
tions, and a history of heavy smoking.
On examination between recurrent crying
spells, his blood pressure was 143/92 with a
regular pulse of 62, and there were no carotid
bruits. His mental status was normal. Cranial
nerve examination disclosed a flattening of
the left nasolabial fold and decreased pin-
prick sensation over his left face with an
occasional mild facial twitching. Cranial
nerves IX-XII were intact, and gag reflex and
palate elevation were normal. He did not have
dysarthria or a brisk jaw jerk. The rest of the
neurological examination showed mild weak-
ness in his left upper arm, and decreased pin-
prick and temperature sensation over the left
half of his body. His reflexes were +2 and
symmetric with downgoing toes.
The patient lacked prior depression, new
depressive symptoms, or prior crying spells as
an adult except for a single episode during
dental anaesthesia. At the time of his admis-
sion, he had not had any recent adverse
events in his life, and was totally surprised by
his reaction.
The patient’s crying spells, paraesthesias,
and neurological findings entirely resolved
within about 3 hours. Routine laboratory
tests, ECG, and CT were normal. Two days
after admission, MRI disclosed a mild degree
of white matter capping over the right frontal
horn, and an EEG showed frontal intermit-
tent rhythmic delta activity but no epilepti-
form changes. Carotid Doppler studies
showed atherosclerotic changes without
haemodynamically relevant obstruction. He
was discharged on antiplatelet therapy with
aspirin.
These results suggest that crying spells can
attack. He presented with paroxysmal crying
spells followed by a left sided hypaesthesia
and a mild left sided weakness, all of which
resolved. His crying was non-emotional,
inappropriate to the context, and did not cor-
respond to his underlying mood. Moreover,
the patient had multiple vascular risk factors
supportive of a cerebrovascular aetiology for
his episode.
The most common cause of pathological
crying is pseudobulbar palsy, a complication
of strokes and other diVuse or bihemispheric
brain damage.1 Pseudobulbar palsy results
from bilateral interruption of upper motor
neuron innervation of bulbar motor nuclei
and brainstem centres. In addition to crying,
pseudobulbar palsy may include dysarthria,
dysphagia, bifacial weakness, increased facial
and mandibular reflexes, and weak tongue
movements. There were no signs or symp-
toms of pseudobulbar palsy in this patient.
255
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
Crying or dacrystic seizures also occur but
are rare. These seizures are part of the range
of complex partial seizures and usually ema-
nate from the right temporolimbic system.2
Crying seizures may result from prior cer-
ebral infarctions.3 Although our patient had
mild twitching of his left face, he did not have
other evidence suggesting definite seizure
activity.
It is likely that this patient had a single
transient ischaemic attack with multiple
crying spells. The localisation of his attack is
unclear; involvement of the right thalamus or
neighbouring internal capsule is a possibility.
Similar to spells of laughter, spells of crying
may occur in relation to unilateral cerebrov-
ascular events. Although most reports of cry-
ing after unilateral strokes have reported left
hemispheric lesions,4 crying also may result
from right hemispheric strokes.4 Even more
similar to our patient, sudden laughing spells,
“le fou rire prodromique,” rarely precede
strokes involving the left capsular-thalamic,
lenticular-caudate, or pontine regions.5 Our
patient may have had a comparable phenom-
enon from the right hemisphere. The mech-
anism for this phenomenon may have been
temporary activation or stimulation of ischae-
mic motor pathways.
MARIO F MENDEZ
YURI L BRONSTEIN
Department of Neurology, University of California at
Los Angeles, West Los Angeles Veterans AVairs Medical
Center, Los Angeles, CA, USA
Correspondence to: Dr MF Mendez, Neurobehav-
ior Unit (691/116AF), West Los Angeles V.A.
Medical Center, 11301 Wilshire Blvd, Los Angeles,
CA 90073, USA. Telephone 001 310 478 3711 ext
42696; fax 001 310 268 4181; email
mmendez@UCLA.edu
1 Dark FL, McGrath JJ, Ron MA. Pathological
laughing and crying. Aus N Z J Psychiatry
1996;30:472–9.
2 Luciano D, Devinsky O, Perrine K. Crying sei-
zures. Neurology 1993;43:2113–7.
3 Wong DZ, Steg RE, Futrell N. Crying seizures
after cerebral infarction [letter]. J Neurol
Neurosurg Psychiatry 1995;58:480–1.
4 House A, Dennis M, Molyneux A, et al.
Emotionalism after stroke. BMJ 1989;298:
991–4.
5 Carel C, Albucher JF, Manelfe C, et al. Fou rire
prodromique heralding a left internal carotid
artery occlusion. Stroke 1997;28:2081–3.
Continuous drop type of orthostatic
hypotension
Orthostatic hypotension has usually been
evaluated for 2–10 minutes after standing.1 2
Multiple system atrophy (MSA: Shy-Drager
syndrome) is one of the neurodegeneratative
diseases which show marked orthostatic
hypotension. We studied changes of blood
pressure for more than 20 minutes after
standing in 30 patients with MSA.
The patients lay down on a tilting table,
and an intravenous cannula was introduced
into the cubital vein more than 30 minutes
before the 25 minute test of 60° head up tilt.
Blood pressure and heart rate were recorded
every minute with an automatic sphygmoma-
nometer. Patients could clearly be classified
into two groups in terms of the time taken to
reach the minimum blood pressure. In 12
patients systolic blood pressure fell rapidly,
reached a minimum within 5 minutes, and
then remained stable or partially recovered
(early drop type); whereas, in 13 patients
blood pressure fell immediately after tilting
but kept decreasing by more than 8 mm Hg
from that at 5 minutes (mean 12.8 mm Hg;
256 Letters, Correspondence, Book reviews

J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
tilt up tilt down graphy, the final conclusion and its interpret-
160 ation require further study.
SBP
We think that more than a 20 minute tilt up
SBP (mm Hg) and HR/min
HR study is needed to evaluate orthostatic hypo-
tension and that reduced endurance of
140
CO exercise and the syncope that occurs some
time after standing should be considered
SVR symptoms of a continuous drop in blood
120 pressure.
NA
TAKANORI YOKOTA
100 KAZUTO MITANI
YUKINOBU SAITO
Department of Neurology

80 TOSHIYUKI ONIKI
Third Department of Internal Medicine,Tokyo Medical
and Dental University, Tokyo 113, Japan
6.0 60
MICHIYUKI HAYASHI
Department of Neurology, Tokyo Metropolitan
Neurological Hospital,Tokyo 183, Japan
CO l/mm

5.0 40 Correspondence to: Dr Takanori Yokota, Depart-

ment of Neurology, Tokyo Medical and Dental
University, 1-5-45 Yushima, Bunkyo-ku, Tokyo
113-8519, Japan. Telephone +81-3-5803-5234; fax
4.0 20 +81-3-5808-0169.

0 1 Mathias CJ, Bannister R. Investigation of

3.0 autonomic disorders. In: Bannister R, Mathias
CJ, eds. Autonomic failure. A textbook of clinical
disorders of the autonomic nervous system. Oxford:
2000 Oxford Medical Publications, 1992:255–90.
2 Low PA. Laboratory evaluation of autonomic
failure. In: Low PA, ed. Clinical autonomic disor-
SVR (dyne.s.cm–5)

ders. New York: Little, Brown, 1993:169–95.

3 Oppenheimer D. Lateral horn cells in progres-
1500 sive autonomic failure. J Neurol Sci 1980;46:
393–404.

1000

500
CORRESPONDENCE
0.2
NA (ng/ml)

0.15
0.1
0.05
0
0 5
Continuous drop type of orthostatic hypotension during 25 minute tilt up in a patient with MSA.
SBP=systolic blood pressure; HR=heart rate; CO=cardiac output; SVR=systemic vascular resistance;
NA=plasma noradrenaline concentration.
maximum 74 mm Hg), taking more than 10
minutes to reach the minimum (continuous
drop type) (figure). The other five patients
could not remain standing for more than 5
minutes because of symptoms of orthostatic
hypotension. No patient showed the sudden
drop in blood pressure and heart rate seen in
vasovagal syncope. In the continuous drop
type, there were no decreases between 5 and
20 minutes in heart rate (+2.3 bpm) and the
noradrenaline (norepinephrine) level (+0.05
ng/ml) during the decrease in blood pressure.
A slight increase in packed cell volume
between 5 and 20 minutes was noted
(mean=1.4%).
Most patients with continuous drop type
orthostatic hypotension reported reduced
endurance for more than 10 minutes of exer-
cise (easy fatiguability). Two experienced
syncope more than 20 minutes after standing.
We used a Swan-Ganz catheter to investi-
gate the haemodynamics in three patients
with orthostatic hypotension of the continu-
10 15 20 25
Time (min)
ous drop type. To prevent the concentration
of plasma, saline of calculated volume was
infused during tilting. During the continuous
decease in blood pressure, cardiac output
proportionally decreased but systemic vascu-
lar resistance did not change (figure).
Our results suggest that in many patients
with MSA the blood pressure drops continu-
ously on standing. The continuous blood
pressure drop is caused by continuous reduc-
tion of cardiac output. A part of the
mechanism for continuous reduction of
cardiac output should be lack of reflex tachy-
cardia and no significant release of noradren-
aline which are caused by interruption of the
baroreflex arc, as is known in MSA.3
However, further explanation, such as con-
tinuous vasodilatation of the volume vessels,
is necessary for the diVerence in mechanisms
between the early drop type and the continu-
ous drop type. As we did not record heart rate
and blood pressure continuously and did not
evaluate ventricular function by echocardio-
Respiratory aspects of neurological
disease
An account of respiratory aspects of neuro-
logical disease, such as the highly informative
one presented,1 would be incomplete without
mention of breathlessness resulting from
neurogenic pulmonary oedema, character-
ised by an “increase in extravascular lung
water in patients who have sustained a change
in neurological condition”.2 Neurological
disorders associated with this syndrome
include subarachnoid haemorrhage, middle
cerebral artery stroke, and cerebellar
haemorrhage.2 Brain stem stroke, acute
hydrocephalus due to colloid cyst of the third
ventricle, closed head injury, and status
epilepticus, were also documented as risk
factors in a literature review by Smith and
Matthay,2 who proposed, on the basis of their
own study, that increased pulmonary vascular
hydrostatic pressure might be a more signifi-
cant aetiopathogenic mechanism than in-
creased pulmonary capillary permeability.2 A
more direct link between neurogenic myocar-
dial damage and pulmonary oedema can be
postulated when subarachnoid haemorrhage
is complicated by reversible severe left
ventricular dysfunction, as documented in
two cases reported by Wells et al.3
O M P JOLOBE
Department of Medicine for the Elderly,
Tameside General Hospital, Fountain Street,
Ashton under Lyne OL6 9RW, UK
Letters, Correspondence, Book reviews
1 Polkey MI, Lyall RA, Moxham J, et al. Respira-
tory aspects of neurological disease. J Neurol
Neurosurg Psychiatry 1999;66:5–15.
2 Smith WS, Matthay MA. Evidence for a hydro-
static mechanism in human neurogenic pulmo-
nary oedema. Chest 1997;111:1326–33.
3 Wells C, Cujec B, Johnson D, et al. Reversibility
of severe left ventricular dysfunction in patients
with subarachnoid haemorrhage. Am Heart J
1995;129:409–12.
Polkey replies:
We thank Dr Jolobe for his interest in our
article; we did not cover neurogenic pulmo-
nary oedema. We agree, however, that it can
be a diYcult clinical problem and therefore
appreciate his contribution.
M I POLKEY
Idiopathic cerebellar ataxia associated
with celiac disease: lack of distinctive
neurological features
Although applauding the contribution of Pel-
lecchia et al1 to the more widespread recogni-
tion of the association between gluten sensi-
tivity and ataxia we disagree that ataxia
associated with gluten sensitivity lacks “dis-
tinctive neurological features”. Both their
data and our own2 indicate that this group of
patients can be distinguished by the late
(non-childhood) onset of gait ataxia with
relatively mild upper limb signs, analogous to
Harding’s group 1.3 Again, coexistent neu-
ropathy is common in these patients, found in
two out of three of the patients of Pellecchia et
al and 21 of our 28.2 We agree that
gastrointestinal symptoms are rare: rather
than entitling their paper “lack of distinctive
neurological features”, perhaps “lack of
distinctive gastroenterological features”
might have been more appropriate!
We were surprised at the high specificity
and sensitivity of increased antigliadin anti-
body titres in their hands. Although we found
both IgA and IgG antigliadin antibodies to be
invaluable screening tools in patients with
ataxia, only 11 of our 28 patients with
increased antigliadin antibodies had histology
of overt coeliac disease on duodenal biopsy,
the remainder having normal or non-specific
inflammatory changes but with an HLA
genotype in keeping with gluten sensitivity. It
is interesting to note that despite the often
quoted high sensitivity for coeliac disease of
increased antiendomysium antibody titres,
such was found in only one of three patients
of Pellecchia et al with coeliac disease. This
concurs with our impression of very modest
sensitivity of antiendomysium antibodies in
gluten ataxia.
Gluten sensitivity is common in patients
with ataxia, and can be identified by in-
creased antigliadin antibody titres in the
presence of appropriate histocompatibility
antigens2. Although the clinical features of
gluten ataxia are not entirely specific, they are
distinctive.
M HADJIVASSILIOU
R A GRÜNEWALD
G A B DAVIES-JONES
Department of Neurology, Royal Hallamshire Hospital,
Glossop Road, SheYeld S10 2JF, UK
Correspondence to: Dr G A B Davies-Jones,
Department of Neurology, Royal Hallamshire Hos-
pital, Glossop Road, SheYeld S10 2JF, UK.
1 Pellecchia MT, Scala R, Filla A, et al. Idiopathic
cerebellar ataxia associated with celiac disease:
lack of distinctive neurological features J Neurol
Neurosurg Psychiatry 1999;66:32–5.
257
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
2 M Hadjivassiliou, R A Grünewald, G A B 2 Hadjivassiliou M, Grunewald RA, Chattopad-
Davies-Jones, et al. Clinical, radiological, neu- hyay AK, et al. Clinical, radiological, neuro-
rophysiological, and neuropathological charac- physiological, and neuropathological charac-
tersitics of gluten ataxia. Lancet 1999;352: teristics of gluten ataxia. Lancet 1998;352:
1582–5. 1582–5.
3 Harding A E. Idiopathic late onset cerebellar 3 Hadjivassiliou M, Gibson A, Davies-Jones
ataxia: a clinical and genetic study of 36 cases. GAB, et al. Does cryptic gluten sensitivity play
J Neurol Sci 1981;51:259–71. a part in neurological illness? Lancet 1996;347:
369–71.
4 Catassi C, Ratsch IM, Fabiani E, et al. Coeliac
Pellecchia et al reply: disease in the year 2000: exploring the iceberg.
Lancet 1994;343:200–3.
We thank Hadjivassiliou et al for their
interesting comments on our paper. They
suggest that patients with gluten ataxia can be
distinguished by the late onset of gait ataxia Procainamide for faecal incontinence in
and the relatively mild upper limb signs. Our myotonic dystrophy
results support the finding of a late onset in
these patients, but this feature cannot be con- We read with interest the article by Aber-
sidered a distinctive one. In fact, in our popu- crombie et al which describes the pathophysi-
lation 11 out of 24 patients with idiopathic
ology and surgical management of faecal
cerebellar ataxia had a late onset, but only
incontinence in two siblings with severe myo-
three of them were aVected by celiac disease.1
tonic dystrophy.1
Furthermore, we do not think that celiac
In the authors’ experience, long term
patients may be distinguished by mild upper
results of both medical and surgical manage-
limb signs and coexistent neuropathy; in our
ment of the faecal incontinence were unsatis-
study 20 out of 24 patients with idiopathic
factory, as proved by the fact that postanal
cerebellar ataxia, including the three patients
sphincter repair restored faecal continence
with celiac disease, had ataxic gait as the pre-
only for a brief time.
senting and prominent clinical feature. Simi-
The authors’ pessimistic conclusions sug-
larly, nerve conduction studies, performed in
gest that “faecal incontinence in myotonic
17 out of 24 patients, showed a peripheral
dystrophy is diYcult to relieve by any
neuropathy in nine, including two out of the
currently available treatment other than
three patients with celiac disease.1
colostomy”. It should be noted, however, that
We understand that some discrepancies
the medical treatment used is not specified in
arise comparing our study with that of Hadji-
the text.
vassiliou et al. Firstly, only six out of their 28
Our experience with medical treatment
patients had evidence of cerebellar atrophy
using procainamide in a patient with severe
on MRI,2 whereas all of our patients had cer-
myotonic dystrophy and faecal incontinence
ebellar atrophy. Secondly, many of their
is less disappointing.2 The patient—a 19 year
patients had a peripheral neuropathy in the
old man—had had his illness diagnosed 4
absence of cerebellar atrophy.2 This finding
years earlier on clinical grounds and electro-
could explain the relatively mild upper limb
physiological and genetic tests. Early symp-
signs. Although two of our three celiac
toms of sphincteric impairment developed
patients had a clinically silent peripheral neu-
soon after, including mild stress urinary
ropathy, we think that their ataxia was
incontinence and minor episodes of poor
explained by cerebellar atrophy. Thirdly, we
control of loose stool.
found a high prevalence (12.5%) of celiac
A complete diagnostic investigation, in-
disease on duodenal biopsy among patients
cluding physical examination, defecography,
with idiopathic cerebellar ataxia,1 whereas
and electrophysiogical tests of pelvic floor
none of the six patients with cerebellar
musculature, was performed. At physical
atrophy described by Hadjivassiliou et al
examination, digital anorectal evaluation
showed histological features of celiac disease.2
showed low squeeze pressures. A reduced
It would be interesting to know the preva-
rectal diameter (4.5 cm), anal gaping, and
lence of gluten ataxia among all ataxic
barium loss at rest were found at defecogra-
patients screened for antigliadin by Hadjivas-
phy. Motor evoked potentials elicited by cor-
siliou et al.
tical and lumbar magnetic stimulation and
Our series is too small to estimate the sen-
recorded from the external anal sphincter3
sitivity of both antigliadin and antiendomy-
showed a normal latency and decreased
sium antibodies in gluten ataxia; unfortu-
amplitude. Somatosensory evoked potentials
nately Hadjivassiliou et al did not report any
after anal stimulation and sacral reflex latency
data on antiendomysium antibody screening
were normal. EMG recording of the external
in their patients. On the other hand, we were
anal sphincter showed, as in the first patient
surprised at the high prevalence of antigliadin
of Abercrombie et al, a decreased number of
antibody positivity (12%) in the normal
motor units and multiple myotonic dis-
population studied by Hadjivassiliou et al in a
charges. Few motor unit potentials presented
previous report.3 This is by contrast with the
polyphasic waveforms and decreased dura-
2% of antigliadin antibody positivity found in
tion and amplitude.
a large population by Catassi et al.4 Further
A regular treatment with procainamide
studies are required to better characterise the
(300 mg twice a day) lead to a dramatic
syndrome of cerebellar ataxia associated with
improvement of both systemic myotonia and
celiac disease or gluten sensitivity.
faecal incontinence. A 13 month follow up
assessment has shown a stable clinical
M T PELLECCHIA
R SCALA improvement. Repeated electrophysiological
A FILLA investigation showed disappearance of myot-
G DE MICHELE onic discharges at the external anal sphincter,
whereas defecography disclosed an improved
P BARONE
Department of Neurological Sciences, Via S Pansini 5, rectal compliance (5.2 cm in diameter) at
80131 Naples, Italy capacity and no more than a barium leak on
straining.
The pathophysiology of motor disorders of
1 Pellecchia MT, Scala R, Filla A, et al. Idiopathic the gastrointestinal tract in myotonic dystro-
cerebellar ataxia associated with celiac disease:
lack of distinctive neurological features. J Neu- phy is still debated and controversial. Histo-
rol Neurosurg Psychiatry 1999;66:32–5. logical study of the external anal sphincter and
258
the EMG pattern in patients with myotonic
dystrophy show a multitude of defects includ-
ing expression of myotonia, myopathy, muscu-
lar atrophy, and neural abnormalities.1 4
The possible management of myotonia and
some of its clinical manifestations, such as
dyspnoea,5 by antimyotonic drugs (disopyra-
mide and procainamide), justifies the use of
the same pharmacological approach in anal
sphincteric dysfunction manifested in a few
cases of myotonic dystrophy.
We conclude that treatment of faecal
incontinence with procainamide should al-
ways be attempted before any surgical option
in patients with myotonic dystrophy.
G PELLICCIONI
O SCARPINO
Department of Neurology, INRCA, Geriatric Hospital,
Ancona, Italy
V PILONI
Department of Radiology, Az. N 7, Ancona, Italy
Correspondence to: Dr Giuseppe Pelliccioni, De-
partment of Neurology, Geriatric Hospital, via della
Montagnola, 164, 60100 Ancona, Italy. Telephone
0039 071 8003432; fax 0039 071 8003530; email:
o.scarpino@fastnet.it
1 Abercrombie JF, Rogers J, Swash M. Faecal
incontinence in myotonic dystrophy. J Neurol
Neurosurg Psychiatry 1998;64:128–30.
2 Pelliccioni G, Scarpino O, Piloni V. Faecal
incontinence in a patient with myotonic
dystrophy: eYcacy of procainamide. Electroen-
cephalogr Clin Neurophysiol 1997;103:125.
3 Pelliccioni G, Scarpino O, Piloni V. Motor
evoked potentials recorded from external anal
sphincter by cortical and lumbo-sacral mag-
netic stimulation: normative data. J Neurol Sci
1997;149:69–72.
4 Eckardt VF, Nix W. The anal sphincter in
patients with myotonic muscular dystrophy.
Gastroenterology 1991;100:424–30.
5 Fitting JW, Leuenberger P. Procainamide for
dyspnea in myotonic dystrophy. Am Rev Respir
Dis 1989;140:1442–5.
Flail arm syndrome or Vulpian-
Bernhart’s form of amyotrophic lateral
sclerosis
We read with interest the article by Hu et al1
concerning flail arm syndrome, a distinctive
variant of amyotrophic lateral sclerosis. The
authors presented a subgroup of patients
aVected by amyotrophic lateral sclerosis that
predominantly showed signs of lower motor
neuron disease in the upper limbs without
significant functional involvement of other
regions upon clinical presentation. This sub-
group of patients is clinically characterised by
the display of progressive atrophy and
weakness in the arms with little eVect on the
bulbar muscles or legs. Atrophy and loss of
strength aVect the upper limb muscles in a
more or less symmetric manner, prevalent in
the proximal muscles. The comparative study
with the rest of the amyotrophic lateral
sclerosis group supplies very interesting
details for the physician, such as a clear
predominance among men, and a longer
median survival. They conclude by suggest-
ing that this syndrome could be a new variant
of amyotrophic lateral sclerosis.
Finally, the authors carry out a historical
review and refer to the fact that this
distinctive amyotrophic lateral sclerosis vari-
ant was probably first described by Gowers in
1888, furnished with exquisite graphic illus-
trations.
To this eVect, we draw attention to prior
descriptions of the same syndrome, reported
by Vulpian2 in 1886, known in Franco-
German literature as Vulpian-Bernhardt’s
form.
In his book Maladies du Système Nerveux
Vulpian described a patient who showed signs
of weakness and symmetric proximal atrophy
of neurogenic origin, and called it chronic
anterior poliomyelitis. The patient showed
symptoms of proximal amyotrophy, and signs
of denervation and upper motor neuron
involvement. Since then, in those countries
and other countries under their influence,3 4
we have come to use the eponym of Vulpian-
Bernhardt’s syndrome to describe those
forms of amyotrophic lateral sclerosis with
more or less symmetric involvement of the
proximal muscles of the upper limbs at the
clinical onset.
A certain enigma exists surrounding the
characteristic distribution of weakness and
muscle atrophy. The reason for the preva-
lence in the proximal muscles of the upper
limbs is unknown. We can furnish little more
information in this respect. However, in the
1960s, in the diVerential diagnosis of this
syndrome, it was proposed that the muscles
predominantly aVected in Vulpian-
Bernhardt’s form were the deltoideus, the
infraespinatus, the supraespinatus, the ster-
nocleidomastoideus, and the teres minor.
The predominant involvement in these mus-
cles permitted its distinction from that previ-
ously called Erb’s dystrophy.5
As a consequence of the atrophy of these
muscles, the upper limbs adopt a characteris-
tic position, with the shoulders slumped, and
the arms, forearms, and hands in pronation.
As the illness progresses, the hand muscles
are aVected, with atrophy of the following
muscles: opponens pollicis, flexor brevis,
abductor pollicis brevis, adductor pollicis,
interossii, and lumbricales, which leads to the
formation of the characteristic Aran-
Duchenne hand.
Obviously, signs of corticospinal involve-
ment with hyperreflexia in the lower limbs
and Babinski’s sign both appear. In the initial
stages of the illness, there is no eVect on the
diaphragm. The presence of signs of involve-
ment of the upper motor neuron, its different
clinical evolution, and the data supplied by
genetic molecular investigation allow us to
distinguish the syndrome previously known
as Vulpian-Bernhardt and now rebaptised as
flail arm syndrome from other motor neuron
syndromes such as of the spinal muscular
atrophies, Kennedy’s disease, multifocal
motor neuropathy, and monomelic amyotro-
phy.
JOSEP GAMEZ
CARLOS CERVERA
AGUSTIN CODINA
Servicio de Neurologia, Hospital Gral Universitari Vall
d‘Hebron, Passeig Vall d‘ Hebron 119–135, 08035
Barcelona, Spain
Correspondence to: Dr Josep Gamez, Servicio de
Neurologia, Hospital Gral Universitari Vall
d‘Hebron, Passeig Vall d‘ Hebron 119–135, 08035
Barcelona, Spain. email 12784jgc@comb.es
1 Hu MTM, Ellis CM, Al-Chalabri AA, et al. Flail
arm syndrome: a distinctive variant of amyo-
trophic lateral sclerosis. J Neurol Neurosurg Psy-
chiatry 1998;65:950–1.
2 Vulpian A. Maladies du système nerveux (moelle
épinière). Vol 2, chapter 23. Paris: Octave Doin,
1886:436.
3 Hurwitz L, Lapresle J, Garcin R. Atrophie mus-
culaire neurogène de topographie proximale et
symétrique simulant une myopathie. Étude de
deux observations. Rev Neurol (Paris) 1961;
104:98–107.
Letters, Correspondence, Book reviews
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
4 Erbslöh F. In: Bodechtel G, ed. DiVerentialdiag-
nose neurologischer Krankheitsbilder, 2nd ed.
Stuttgart: Georg Thieme Verlag, 1963:676–
701.
5 Hallen O. Das Verteilungsschema der scapulo-
humeralen Formen chronisch progressiver
myatrophischer Erkrankungen. Ein Baitrag zur
klinischen DiVerentialdiagnose der Erbschen
juvenilen Muskeldystrophie und des Typus
Vulpian-Berhardt der spinalen progressiven
Muskelatrophie. Deutsche Zeitschrift für Nerven-
heilkunde 1966;188:1–11.
Pain after whiplash
This latest study from Lithuania1 is an
answer to many questions—namely, that the
previous diYculties that these researchers
had with identifying the late whiplash
syndrome in Lithuania is that they were not
looking “in the right place”. As it turns out,
the problem is that Lithuanians simply are
not behaving the way many in western coun-
tries expounding myths of whiplash would
like. There are some methodological issues
which can be considered, as below, but the
lesson of discarding “unsightly” data because
it is too disturbing to one’s personal view and
vested interest in the whiplash controversy
has already been taught elsewhere.2 SuYce it
to say that the truth has been laid bare and
we (those of us struggling with epidemic
proportions of the late whiplash syndrome in
our own countries) now need to enlighten
ourselves and put this data to practical use in
helping whiplash patients rather than resist-
ing the inevitable.
After completion of the first historical
cohort study, this more recent study selects
an entirely separate, distinct sample of these
“misbehaving” Lithuanians, but in a more
intriguing fashion. This is the first true
inception cohort study wherein people who
have not been preselected by their attendance
at emergency departments, or contaminated
by therapists or lawyers, can be studied to
appreciate the natural evolution of the injury
which underlies whiplash associated dis-
orders grades 1 and 2. This is the study’s
greatest strength. The study has, however, its
limitations.
The first consideration is that there were
98 accident victims who reported acute
symptoms, and thus were at risk for the late
whiplash syndrome. How does this compare
with other studies documenting the natural
evolution of the late whiplash syndrome?
The Swiss study may be useful for compari-
son because it too has only 117 subjects, yet
is much quoted. Setting aside for the
moment that the Swiss study is hampered by
the selection atrocity of advertising for
subjects, and has a host of other reportedly
fatal faults3, and giving some benefit of the
doubt, the study is said to be an accurate
representation of the state of aVairs in Swit-
zerland at that time. Yet, in Switzerland, not
even 60% manage to recover fully by 3
months and many of these were reporting
total disability during that time, whereas the
Lithuanians fully recover in 4 weeks or less,
with little or no therapy, and no disability.
Studies in other western countries disclose
an even greater contrast, with 50%–70% of
patients reporting pain even after 3–6
months, despite the fact that all these studies
are examining the same grades (1 and 2) of
whiplash associated disorders.4 5 Thus, while
the sample size is small in this Lithuanian
study, it is comparable with others reporting
the prognosis of whiplash, and yet gives a
diVerent picture of outcome.
Letters, Correspondence, Book reviews
A second consideration is that perhaps
these Lithuanians are in very minor colli-
sions. True, some of their vehicles were com-
pletely wrecked, but perhaps the vehicles
were not very good quality and so were easily
damaged. Perhaps that is why this cohort had
such a good outcome and only minor injuries.
This is an unhelpful consideration however,
as studies in Canada have shown that those
with absolutely no vehicle damage, in very
low velocity collisions, are just as likely to
report chronic pain as those in more severe
collisions.4 5 Lithuanians seem to behave
appropriately then for minor collisions (if that
is what they indeed had), but Canadians seem
unable to behave appropriately. Again, an-
other cultural rift in the rate of recovery from
whiplash injury is demonstrated.
Thirdly, there are sex diVerences and even
diVerences in seat belt usage between this
population and some others, but even then, it
does not seem to matter what sex, age, and
use of seat belts there is in other western
countries, none of these preclude chronic
pain. In Lithuania, those who were female,
and who did not wear seat belts, still insisted
on behaving as the rest of the cohort.
Finally, perhaps the Lithuanians simply
refuse to report their chronic pain, and
chronic pain cannot be studied in other
cultures in this way. The Lithuanians have no
reluctance to report acute pain, but perhaps
for some reason wish to “suVer in silence” in
spite of chronic pain and disability. This
would be a potential flaw if it was not simul-
taneously shown in this study that the general
Lithuanian population reports the same
prevalence, frequency, and character of neck
pain and headache as does the general popu-
lation in western countries.1 6 If there were
study design barriers to identifying symp-
toms, the control population would have
grossly underreported their symptoms. In-
deed, chronic pain can and is reported by
studies in many diVerent cultures and
languages, including Japan, France, Italy, and
others. If researchers in these non-English
speaking populations can use simple ques-
tionnaires to document the late whiplash
syndrome so eVectively there, then the same
should be possible in Lithuania.
And so, despite the potential limitations of
this study as outlined, there is no way to get
around the stark realisation that the natural
history of the acute whiplash injury in
Lithuania is a benign syndrome with 4 weeks
or less of pain. Equally compelling is the fact
that Lithuania is not the only place where
researchers are having diYculty identifying
epidemics of chronic pain. Recovery from
acute whiplash injury without neurological
injury or fracture routinely occurs within 4–6
weeks in Germany4 and Greece.5 The time
has thus come for a reconciliation of these
epidemiological observations with our own
experience of late whiplash syndrome in
western countries. The truth has been laid
bare and it is our responsibility to utilise this
truth to help prevent the chronic pain and the
suVering we otherwise encounter.7 8
R FERRARI
12779-50 Street, Edmonton,
Alberta, T5A 4L8 Canada
1 Obelieniene D, Schrader H, Bovim G, et al. Pain
after whiplash: a prospective controlled incep-
tion cohort study. J Neurol Neurosurg Psychiatry
1999;279:84.
2 Ferrari R, Russell AS. Whiplash: heading for a
higher ground. A point of view. Spine 1999;24:
97–8.
3 Kwan O, Friel J. A comment on Radanov BP.
Common whiplash: research findings revisited
[letter]. J Rheumatol 1999;26:1205−6.
4 Bonk A, Ferrari R, Giebel GD, et al. A prospec-
tive randomized, controlled outcome study of
two trials of therapy for whiplash injury.
Journal of Musculoskeletal Pain 1999 (in press).
5 Partheni M, Constantoyannis C, Ferrari R, et al.
Prospective cohort outcome study of whiplash
injury in Greece. Journal of Musculoskeletal Pain
1999 (in press).
6 Obelieniene D, Bovim G, Schrader H, et al.
Headache after whiplash: a historical cohort
study outside the medico-legal context. Cepha-
lalgia 1998;18:559–64.
7 Ferrari R. The whiplash encyclopedia. Gaithers-
burg, Maryland: Aspen, 1999 (in press).
8 Ferrari R, Kwan O, Russell AS, et al. The best
approach to the problem of whiplash? One
ticket to Lithuania, please. Clin Exp Rheumatol
1999 (in press).
BOOK REVIEWS
Management of Acute and Chronic
Pain. Edited by Narinder Rawal. (Pp 230).
Published by BMJ Books, London 1998.
ISBN 0-7279-1193-7.
This book purports itself to be a comprehen-
sive reference. Certainly the title would
suggest so. However, it is clear that this is not
a comprehensive text, but a book that is an
update on particular timely topics in the field
of pain medicine. There are sections on pain
mechanisms with a chapter on the pharma-
cology of acute and chronic pain, and other
chapters on postoperative pain, obstetric
pain, and acute paediatric pain. There are
three further chapters specifically on the
management of chronic low back pain, cancer
pain, and an overview of interventional pain
techniques.
Many of the authors are internationally
known and this is perhaps the book’s strong-
est point—one does get a state of the art
review and to this end I warmly welcome this
book as an addition to the bookshelf to
update a busy anaesthetist or pain specialist,
though the chapters on chronic low back pain
and cancer pain will also be of interest to
those in other fields.
The chapter on the anatomy and physiol-
ogy of pain is excellent in that it has clear
explanations and a number of very helpful
diagrams. Unfortunately it fails to mention
increasing understanding of the role of
GABA in mediating analgesia within the spi-
nal cord and furthermore does not mention
some of the other neuroplastic changes which
are well known to occur in chronic pain states
such as central sprouting and phentypic
switching.
The chapter on pharmacology of acute and
chronic pain again is well written, but unfor-
tunately a lot of time is spent on non-steroidal
drugs. There is a review of the adjuvant drugs
such as antidepressants and anticonvulsants
that are used in chronic pain, however one is
left at the end with a sense of knowing about
the drugs but not quite when to use them.
There is no mention of the increasing use of
gabapentin nor of other drugs that are some-
times used in chronic pain states such as clo-
nidine and other sympatholytic agents or cal-
cium channel blockers.
259
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The chapter on acute postoperative pain
management is well written and informative
as are the chapters on obstetric and paediat-
ric pain. The chapter on chronic low back
pain by Rauck is one of the best I have seen
for some time. It is a comprehensive review of
both acute and chronic low back pain. It is
excellent as it also mentions treatments that
are often performed outside the medical spe-
cialist arena. I was pleased to see in it the
mention of some of the newly evolving tech-
niques such as facet denervations, spinal cord
stimulation, and disc denervation. It was a
pity that the randomised control trials which
have shown facet denervation to be an
outstandingly useful technique in chronic low
back pain were not mentioned. It was also a
pity that the reference to the disc denervation
procedure was to another text book rather
than any original papers.
The chapter on cancer pain management
has been written by internationally known
authors and is an excellent summary of the
subject. In the section on interventional pain
techniques the emphasis was on spinal cord
stimulation, radiofrequency, and cryoneu-
rolysis. Again this chapter has been written by
an internationally well known author who
concentrated on general overview of the
techniques rather than a how to do it
approach, which I think one would have to go
to a bigger text for. In summary I think that
this volume would make an excellent addition
to the bookshelf of those involved in the
treatment and management of pain.
RAJESH MUNGLANI
Neuropathology of Dementing
Disorders. Edited by WILLIAM R MARKESBERY.
(Pp 405, £125.00). Published by Edward
Arnold, London, 1998. ISBN
0-340-59037-8.
This is a really excellent book which is both
comprehensive and amazingly up to date,
with the inclusion of many references from as
late as 1997.
As a clinical neurologist and neuropsy-
chologist with a longstanding interest in the
dementias, I found it extremely valuable. The
editor has done a very good job in posing a
coherence, format, and style, which is often
lacking from multicontributor textbooks.
The title of the book is perhaps a little mis-
leading in that the book includes, as well as
traditional neuropathology, a very compre-
hensive overview of the molecular biology
and genetics of the dementias. As would be
expected, a considerable proportion of the
book is dedicated to Alzheimer’s disease with
chapters on both the clinical features, genet-
ics, and the neuropathology. The frontotem-
poral dementias are also well covered and the
book includes a chapter on the recent devel-
opments related to chromosome 17 linked
dementias. There are also sections on pro-
gressive supranuclear palsy, Huntington’s
disease, corticobasal degeneration, dementia
with lewy bodies, and prion diseases and vas-
cular dementia.
The editor has managed to persuade many
of the world’s experts to contribute. For
instance, the chapter on prion diseases is by
D’Almond and the recent Nobel laureate
Prusiner, and the frontotemporal dementias
are reviewed by Brun and Gustafson. Genet-
ics of Alzheimer’s disease are dealt with by St
George-Hyslop and the neuropathology of
Alzheimer’s disease by Price and coworkers.
260
The standard of illustrations is excellent
and the style generally very readable. I shall
certainly find it extremely useful as a work of
reference and for teaching purposes. The
editor is to be complimented on producing
such a delightful work.
JOHN HODGES
Instrumented Spinal Surgery.
Principles and Technique. Edited by
JÜRGEN HARMS and GIUSEPPE TABASSO. (Pp
198, DM248.00). Published by Georg
Thieme Verlag, Stuttgart 1999. ISBN
3-13-110761-8.
I very much enjoyed reviewing this textbook of
instrumented spinal surgery written by
Giuseppi Tabasso under the auspices of Jürgen
Harms. Dr Harms is well known to all spinal
surgeons and has made a very important con-
tribution to the development of spinal surgery
over the past 20 years, based on strong
personal convictions. Many surgeons who
manage spinal disorders would not choose to
implement all of Professor Harms’ solutions
but all who have a serious interest in the surgi-
cal treatment of the spine admire and are
grateful for his contribution. Within this book
spinal surgeons will find a rational and practi-
cal approach which will allow them to treat a
wide range of spinal disorders according to
well thought out principles.
The opening chapter describes spinal
biomechanics under normal and pathological
circumstances mainly by using easily under-
stood drawings and diagrams. Some of these
drawings reminded me of images that I have
recently seen on an interactive CD ROM that
I bought for my 4 year old son. This is not a
criticism and I fully support any attempt to
simplify the science of biomechanics which is
often cloaked in seemingly contradictory jar-
gon. Most spinal surgeons will be able to
assimilate the two basic principles which
underpin much of instrumented spinal
surgery— namely, that the anterior column
resists load compression forces and that the
posterior column acts as a tension band
which when disrupted should be reconsti-
tuted in compression. The remaining chap-
ters cover fracture management, late kypho-
sis, metastatic tumours, spondylolisthesis,
degenerative spinal disease, and infection.
Each chapter sets out the principles of
management which are illustrated schemati-
cally. There then follow case studies illus-
trated by radiological images including CT
and MRI. These have reproduced well and
surgeons will admire the technical precision
and excellent anatomical reductions illus-
trated by these clinical cases. It is, however, a
source of constant annoyance to spinal
surgeons that perfect postoperative films do
not always correlate with good clinical results
and this discrepancy remains a source of fas-
cination and mystery.
It is in the degenerative spine that this dis-
crepancy between radiological and clinical
findings is most apparent and it is partly for
this reason that the management of these
conditions is often controversial. It is diY-
cult to disagree with much of the logic
presented by the authors in planning their
interventions but there is a danger that inex-
perienced surgeons may be misled into
adopting complex solutions when often more
simple operations will suYce. The authors’
description of their approach to failed back
surgery syndrome illustrates this problem
and the inadequacies of attempting to treat a
complex clinical problem by focusing on one
aspect of it.
This book will be a useful addition to the
shelves of spinal surgery textbooks and many
orthopaedic and neurosurgical departmental
libraries will wish to buy a copy.
RODNEY LAING
Surgical Disorders of the Peripheral
Nerves. Edited by R BIRCH, G BONNEY, and
C B WYNN PARRY. (Pp 539, £95.00). Published
by Harcourt Brace and Co Ltd. London
1998. ISBN 0 443 04443 0.
I wondered, when I received this book, how I
Letters, Correspondence, Book reviews
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.254 on 1 August 1999. Downloaded from http://jnnp.bmj.com/ on 3 April 2019 by guest. Protected by copyright.
could possibly say anything adverse about a
book written by three such world renowned
experts. I have heard them all lecture often
and have seen them all at work. They have a
vast knowledge and experience of treating
disorders of peripheral nerves. In clinic and
the operating theatre, they have shown
myself and many trainees a clarity in their
planning of management of complex prob-
lems that humbles one’s own thoughts. That
clarity has continued in this text book of over
500 pages. The field of peripheral nerve sur-
gery is covered comprehensively, commenc-
ing with descriptions of anatomy, physiology,
and pathological reaction to injury. This is
followed in subsequent chapters with de-
scriptions of approaches to virtually all the
main peripheral nerves, and the operative
management of brachial plexus injury and
outcomes is covered in three detailed chap-
ters. These are followed by chapters on nerve
entrapment, neuropathy, iatropathic injury,
and neoplasm within the peripheral nerve.
The final section covers electrodiagnosis,
pain, nerve recovery, reconstruction tech-
niques, and rehabilitation.
The text is well written, easy to read, and
supplemented by some excellent line draw-
ings similar to those used in Lundborg’s text.
There are detailed plates showing histology
and various imaging techniques. Each chap-
ter is comprehensive, containing important
historical aspects as well as up to date
techniques, and there is an extensive refer-
ence section. I would recommend that train-
ees of all specialties dealing with peripheral
nerve injuries should read much of this text
and it would be extremely useful as a regular
reference. It would also make an important
and necessary addition to most medical
libraries. All clinicians would be well advised
to read the chapters on iatropathic injuries,
not only for the extensive causes of such inju-
ries encompassing all medical and surgical
departments, but also for the précis of the
changes occurring in medical negligence
claims. This text represents good value for
money.
IAN WHITWORTH